# Targeting neutrophil clearance to harness myeloid responses for wound healing.

> **NIH NIH R01** · UPSTATE MEDICAL UNIVERSITY · 2024 · $158,763

## Abstract

Targeting neutrophils to harness myeloid responses for wound healing
Chronic wounds represent a significant health problem in the United States. Delayed or non-resolving
inflammation is a hallmark of the chronic wound and is sustained by myeloid cell accumulation and upregulated
myelopoiesis. Metabolic conditions such as obesity contribute to this growing problem and influence myeloid
response to wounds. The central hypothesis of this proposal is that obesity and diabetes dysregulate myeloid
responses and thereby impairs wound healing. Our preliminary study using mouse models suggests a
mechanistic link of neutrophil clearance in the bone marrow with myelopoiesis. We propose a translational study
involving both mouse models and human specimens with three Specific Aims: In Aim 1, we will determine the
mechanism by which neutrophil clearance in the bone marrow regulates myelopoiesis, with the hypothesis that
neutrophils release extracellular vesicles that regulate myelopoiesis during their clearance. In Aim 2, we will
determine the mechanism of inhibited neutrophil clearance in the bone marrow in chronic wounds and obesity,
with the hypothesis that chronic wounds and obesity increase glutamine utilization in neutrophils and inhibit their
clearance in the bone marrow. In Aim 3, we will bioengineer a nano-drug that target neutrophils and modify
myeloid response. To achieve this, we will utilize a well-defined versatile telodendrimer to selectively deliver
glutaminase inhibitor to neutrophils and will test the nano-drug in the preclinical mouse model of impaired wound
healing in obesity. The proposed experiments will improve knowledge of myeloid responses during wound
healing. The impact of these studies lies in the potential for translation to therapies that stimulate healing
responses in hard-to-heal wounds. Also, the studies could lead to the development of assays that involve
monitoring blood neutrophil survival as cellular biomarkers to aid in the selection of treatment options for patients
with chronic wounds and/or obesity.
Project Summary/Abstract

## Key facts

- **NIH application ID:** 11096841
- **Project number:** 3R01GM144624-02S1
- **Recipient organization:** UPSTATE MEDICAL UNIVERSITY
- **Principal Investigator:** Norifumi Urao
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $158,763
- **Award type:** 3
- **Project period:** 2023-09-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11096841

## Citation

> US National Institutes of Health, RePORTER application 11096841, Targeting neutrophil clearance to harness myeloid responses for wound healing. (3R01GM144624-02S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11096841. Licensed CC0.

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